As quickly disintegrating preparations in the oral cavity, quickly disintegrating tablets in the oral cavity, chewable tablets, and fine granules, granules, powders and the like which are imparted with quickly disintegrating property in the oral cavity may be exemplified. Among them, the quickly disintegrating preparations in the oral cavity is a dosage form which has been drawing attention in recent years from the viewpoint of its user-friendness, because it can be taken easily even by a patient who has a difficulty in swallowing, and it can be taken without water. However, being a dosage form which is immediately disintegrated in the oral cavity, there is still no bitterness masking technique for the quickly disintegrating tablets in the oral cavity which is considered to be sufficient for a drug having an unpleasant taste, particularly a strong bitterness.
Since quickly disintegrating preparations in the oral cavity is not accompanied by drinking of water and a remaining period of time of the drug in the oral cavity is long, control of sufficient drug dissolution at an early stage after its administration, namely strict control in comparison with conventional preparations which are taken with water, is required. In addition, since quickly disintegrating preparations in the oral cavity are positioned in many cases as a dosage form which improves the properties when the conventional tablets which are already on the market are taken, not only the instant suppression of unpleasant taste in the oral cavity, but also the ensuring of bioavailability when made into an quickly disintegrating preparations in the oral cavity, or the ensuring of bioequivalence with conventional pharmaceutical preparations, are very important in guaranteeing their qualities, so that it is also necessary to assure quick drug dissolution when the preparation is transferred from the oral cavity into gastrointestinal tracts. Thus, it is evident that the conventionally known technique of merely adding a flavor, a sweetener and the like cannot fully cope therewith, and it is extremely difficult to apply the conventionally known film coating method or the like which uses a polymer base material, which is not assumed to be applied to quickly disintegrating preparations in the oral cavity but merely has an object of suppressing unpleasant taste for only dozens of seconds after the administration, directly to the quickly disintegrating preparations in the oral cavity for the aforementioned purpose.
As a technique which is applicable to quickly disintegrating preparations in the oral cavity, International Publication WO 02/96392 discloses, regarding bitterness suppression of a drug having high water-solubility, an invention on a drug-containing microparticles to which a film coat of a combination of a water-insoluble polymer with a water-soluble polymer is applied. Ethyl cellulose, an enteric base material hydroxypropylmethylcellulose phthalate or hydroxypropylmethylcellulose succinate, or the like is used as the water-insoluble polymer of said invention. When the approximately neutral pH in the oral cavity is taken into consideration, selection of an enteric base material is not desirable, because it leads to the leaking of the bitterness. Also, since the dissolution rate described in Examples include those which are lower than 70 to 80% in 30 minutes, there is a room for further improvement when the aforementioned viewpoint of assuring bioequivalence is taken into consideration.
In addition, International Publication WO 2005/039542 discloses a drug-containing coated microparticles for quickly disintegrating tablets in the oral cavity, in which a microparticles containing a drug having an unpleasant taste is coated with a film comprising (1) a pH-independent water-insoluble polymer wherein its ratio in the film is 60% or more and less than 80% and (2) a pH-independent water-soluble substance wherein its ratio in the film is larger than 20% and 40% or less. Said invention relates to a technique on a coated microparticles suited for the suppression of unpleasant taste of a drug, which is a microparticles having an average particle size of 350 μm or less applicable to quickly disintegrating tablets in the oral cavity, that achieved sufficient dissolution suppression in the oral cavity and quick dissolution after transfer into the stomach by the combination of a water-insoluble polymer and a water-soluble substance which do not undergo influence of pH. However, there is still a room for improvement regarding suppression of unpleasant taste when a drug is used in combination with a specific additive agent.
Thus, an object of the present invention is to provide a drug-containing coated microparticles which does not undergo influence of pH, sufficiently suppresses instant unpleasant taste in the oral cavity and quickly show dissolution of the drug after transfer into gastrointestinal tracts, in the aforementioned technique of coated microparticles, even when the drug and a specified additive agent are used, for example, when solifenacin or a salt thereof and polyethylene glycol are used, as well as to provide a production method thereof.